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Endothelin‐1‐induced ET A receptor‐mediated nociception, hyperalgesia and oedema in the mouse hind‐paw: modulation by simultaneous ET B receptor activation

2000; Wiley; Volume: 129; Issue: 5 Linguagem: Inglês

10.1038/sj.bjp.0703154

ISSN

1476-5381

Autores

Anna Paula Piovezan, Pedro DʼOrléans-Juste, Glória Emília Petto de Souza, Giles A. Rae,

Tópico(s)

Ion channel regulation and function

Resumo

Endothelin‐1 causes ET A receptor‐mediated enhancement of capsaicin‐induced nociception in mice. We have assessed if this hyperalgesic effect of endothelin‐1 is also accompanied by other pro‐inflammatory effects, namely nociception and oedema, and characterized the endothelin ET receptors involved. Intraplantar (i.pl.) hind‐paw injection of endothelin‐1 (0.3–30 pmol) induced graded nociceptive responses (accumulated licking time: vehicle, 20.5±3.3 s; endothelin‐1 at 30 pmol, 78.1±9.8 s), largely confined to the first 15 min. Endothelin‐1 (1–10 pmol) potentiated ipsilateral capsaicin‐induced (0.1 μg, i.pl.; at 30 min) nociception (vehicle, 40.2±2.6 s; endothelin‐1 at 10 pmol, 98.4±5.8 s, but 30 pmol was inactive), and caused oedema (increase in paw weight 5 min after capsaicin: vehicle, 46.3±2.3 mg; endothelin‐1 at 30 pmol, 100.3±6.1 mg). Selective ET B receptor agonists sarafotoxin S6c (up to 30 pmol) and IRL 1620 (up to 100 pmol) were inactive, whereas endothelin‐3 (up to 30 pmol) induced only modest oedema. ET A receptor antagonists BQ‐123 (1 nmol, i.pl.) or A‐127722‐5 (6 μmol kg −1 , i.v.) prevented all effects of endothelin‐1 (10 pmol), but the ET B receptor antagonist BQ‐788 (1 or 10 nmol, i.pl.) was ineffective. BQ‐788 (10 nmol, i.pl.) unveiled hyperalgesic effects of 30 pmol endothelin‐1 and endothelin‐3. Sarafotoxin S6c (30 pmol, i.pl.) did not modify endothelin‐1‐induced (10 pmol) nociception or oedema, but abolished hyperalgesia. Thus, endothelin‐1 triggers ET A receptor‐mediated nociception, hyperalgesia and oedema in the mouse hind‐paw. Simultaneous activation of ET B receptors by endothelin‐1 or selective agonists can limit the hyperalgesic, but not the nociceptive or oedematogenic, effects of the peptide. British Journal of Pharmacology (2000) 129 , 961–968, doi: 10.1038/sj.bjp.0703154

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